Six SUND researchers get DKK 60 million to exciting projects

Hallas-Møller Emerging Investigator

Signe Mathiasen, Assistant Professor

Department of Biomedical Sciences

Title: Uncovering the spatiotemporal organization of the adhesion GPCR ADGRL3 and its trans synaptic signaling partners at the single molecule level

Grant amount: DKK 9.997.040

In Denmark, the burden of psychiatric and mental disorders has been predicted to constitute 25% of the public health problems and the consequences of mental illnesses is both highly afflictive to individuals and of great cost to society.

Signe Mathiasen explains: In this project, we study a new and novel receptor target in mental health, the adhesion G protein-coupled receptor latrophilin 3 (ADGRL3), which is implicated in attention-deficit/hyperactivity disorder (ADHD) and other psychiatric disorders that involve dopamine dysfunction, such as schizophrenia. Specifically, the goal is to map the dynamic localization of ADGRL3 receptors in the cell membrane and to correlate its movements to interaction partners out-side and in-side the cell. This will enable us to determine how, where and when ADGRL3 function as a signaling unit with its key synaptic interaction partners. Such basic understanding can help uncover the potential of ADGRL3 as a novel drug target for new and improved pharmacotherapies in e.g. ADHD.

Signe Mathiasen moved back to Denmark in 2020, after working as a scientist for seven years at Columbia University. She is currently employed at the Department of Biomedical Sciences, University of Copenhagen, where she will establish her independent research group from 1 April 2024.

Ascending Investigator BBM

Andrew Blackford, Associate Professor

Department of Cellular and Molecular Medicine

Title: Mechanisms and Targeting of RecQ Helicases in Cancer

DNA is found in every cell in our bodies and encodes the blueprints that make us what we are. Although DNA is relatively stable, there are ways it can become damaged so that bits of it are lost or changed so that it no longer works the way it should. Common sources of DNA damage include ultra-violet rays from the sun and by-products that come from what we eat, drink, or breathe in, such as alcohol and tobacco smoke. In fact, DNA is damaged so often that our cells have evolved to produce proteins that are able to repair it. One set of proteins that helps do this is called the RecQ helicases.

We know that RecQ helicases play an important role in our bodies because when they are mutated, this can lead to syndromes associated with increased cancer risk, premature ageing, and a faulty immune system. The aim of this proposal is to investigate how the RecQ family of helicases functions at the molecular level, which is still relatively poorly understood but is very important for human health.

Grant amount: 9.997.562 DKK

Nicholas Taylor, Associate Professor

Novo Nordisk Foundation Center for Protein Research

Title: Bacteriophage defense at the membrane: structure, function and beyond  

Grant amount: 10.000.000 DKK

Not only humans have viruses that can attack them but also bacteria are under constant attack by viruses, which are known as bacteriophages. In fact, bacteriophages are the most abundant biological units on the planet. Since bacteriophages can kill bacterial cells, they have been used as an alternative to antibiotic therapies to treat bacterial diseases in humans.

It has quite recently been discovered that, like humans, bacteria also have immune systems that protect them against their viruses. How this occurs is however much more poorly understood. I plan to investigate this by looking with very advanced microscopes at these systems and trying to unravel how they work at the molecular level. Furthermore, we will take the first steps to try to make novel applications based on the fundamental mechanisms that we discover, which could ultimately lead to novel application in biomedicine or biotechnology.

Rune Berg, Associate Professor

Department of Neuroscience

Title: Pulling the strings: The brain-spinal machinery that generates movement sequences in health and disease

Grant amount: 10.000.000 DKK

Rune Berg says: Every day, we elegantly and effortlessly move our bodies. The brain generates the commands to contract muscles and, in this way, orchestrates the motion. But how do our brains do it? It is a fundamental part of our lives, yet we do not understand the roots and the mechanisms of how even seemingly simple movements, like walking and reaching for a cup, are produced. In this research proposal, we will investigate how different brain regions communicate with the spinal cord to produce movement sequences using new techniques. This will provide unique and crucial information to understand the nervous system, and how signals propagate across regions. Understanding the foundation of these neural circuits will not only satisfy our curiosity on how we move, but it may also explain the impact of circuit disruption from stroke or spinal cord injuries. This could introduce a path forward for a new clinical therapy for conditions where the motor circuitry is affected, like spinal cord injury and stroke.

Distinguished Investigator BBM

Jakob Nilsson, Professor

Novo Nordisk Foundation Center for Protein Research

Title: Mechanisms of protein phosphatase regulation and their role in cellular signaling  

Grant amount: 9.995.341 DKK

Jakob Nilsson says: Human health depends on our cells’ ability to respond to changes in the environment and the ability of cells to communicate within and with each other. Such cell signaling and communication depend on a chemical process whereby enzymes add or remove a so-called phosphate group from a protein. Thus, addition and removal of phosphate groups from proteins are fundamental signaling mechanisms that are often deregulated in human disease.  Understanding how the enzymes that add or remove phosphates are regulated will reveal fundamental insight into cell function and will provide a new perspective on human diseases. In this project, we will use a new method we have developed to identify and characterize how the enzymes that removes phosphates are regulated. We will use sophisticated cell biological and biochemical methods to understand how these new regulatory mechanisms impact on cellular function to potentially uncover novel disease-causing mechanisms.

Jakob Nilsson is Professor and Group leader at the Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.

Emerging Investigator - Endocrinology and Metabolism

Lærke Gasbjerg, adjunkt

Department of Biomedical Sciences

Title: Mechanistic and therapeutic investigations of splanchnic blood redistribution

Grant amount: 9.998.511 DKK

When you eat, food is digested by the intestines and transferred to the blood. The blood stream transports the digested food to organs of your body which for example need food as an energy source. Eating is therefore essential and when you eat, the blood volumen is increased in the abdominal area to support the digestion and transport digested food. But for some people, this phenomenon leads to symptoms such as dizziness, raised pulse, and fainting. They suffer from low blood pressure called postprandial hypotension and are challenged by eating due to the invalidating symptoms. With this Novo Nordisk Foundation Investigator Grant, I will establish my research group at University of Copenhagen and Rigshospitalet (Copenhagen) and study blood volumen changes in two patient groups with modern imaging techniques (MRI) and also, study the mechanism as well as evaluate treatment options in animals based on hormones that we know are related to blood volume changes during eating.